Hypergammaglobulinemia: Causes, Symptoms, and Treatment

The JAMA Internal Medicine, a journal of the American Medical Association, had published a research paper in 1966 that gives details of a family which suffered from 4 consecutive generations of hypergammaglobulinemia.

Hypergammaglobulinemia is a type of rare immunoproliferative disorder in which the immune system produces excessively high amounts of gamma globulin―a specific class of antibodies. This medical condition is typically marked by abnormally high levels of antibodies circulating in the bloodstream.

There are different types of gamma globulins, and the ones that are checked for diagnosing hypergammaglobulinemia are immunoglobulins (IgS). In this hereditary condition, the level of immunoglobulin M (IgM) is abnormally high. IgMs are Y-shaped proteins generated by B cells to combat infections.

However, in case of hypergammaglobulinemia, there are problems with B cell function, which results in excess production of IgM.

Most cases of hypergammaglobulinemia, apart from showing high levels of IgM, are characterized by low production of other types of immunoglobulins (antibodies). Thus, patients tend to have low levels of IgA, IgG, and IgE. In some patients, only the level of IgM is abnormally high, while the other main immunoglobulins are in the normal range.

Types of Hypergammaglobulinemia

Class switching in B cells is an important biological mechanism that enables them to produce different types of antibodies to combat various infections.

However, in hypergammaglobulinemia, B cells are unable to switch classes, resulting in excess production of just one type of antibodies, known as IgM antibodies. Depending upon the cause of B cells being unable to undergo class switch, hypergammaglobulinemia is classified into the following types:

Type 1

It is observed that T cells induce class switching in B cells. However in this type, T cells are unable to communicate with B cells to undergo class switching.

Type 2

The AICDA gene plays a critical role in the class switching process of B cells. In this type, the mutation of AICDA gene, prevents recombination of genetic material, which is necessary for changing a specific portion of B cell to switch to another type of antibody.

Type 3

In this type, although T cells transmit the message to initiate class switching in B cells, it is not received by the B cells

Type 4

The exact cause of this type is yet to be identified, but this type is marked by over production of IgM, while other immunoglobulins are in the normal range.

Type 5

The UNG gene is critical for class switching of B cells. This gene sends signals to living cells to produce a specific enzyme that assists in gene conversion during somatic recombination in B cells. In this type, there is a mutation of UNG gene, which causes the enzyme to malfunction.

As a result, partial gene conversion occurs, which prevents class switch recombination of B cells.

Symptoms

One may think that the presence of excessive antibodies, like IgM, in hereditary conditions like hypergammaglobulinemia, may actually protect the body from bacteria, viruses and other disease-causing organisms. Unfortunately, a person affected with this condition is vulnerable to a wide range of infections.

The excess production of IgM actually severely compromises the immune system.

To put it simply, low immunity is commonly associated with this medical condition. Hypergammaglobulinemia can make it very difficult to manage some minor infections such as common cold. Thus, lesser infections that are not a cause for concern in otherwise healthy people, can become quite serious in patients affected with hypergammaglobulinemia.

For instance, common cold may turn into full blown bronchitis or pneumonia in people affected with this condition.

Individuals with this condition tend to have chronic infections, such sinusitis, and suffer from serious lung infections such as tuberculosis and pneumonia frequently. Some even feel sick 24/7, which can completely disrupt their day-to-day routine.

Other symptoms that have been linked to this hereditary condition are given below:

• Fatigue
• Anemia
• Enlargement of the spleen, liver, lymph nodes, and tonsils
• Stiffness in joints such as knees and hips

Causes
Chronic ailments, particularly those that target the immune system, are responsible for causing hypergammaglobulinemia. They are mentioned below:

• HIV/AIDS
• Hepatitis C
• Rheumatic diseases
• Cirrhosis

Treatment
Immunoglobulin (IgG) replacement therapy may be recommended for people affected with this condition. IgG antibodies act as the first line of defense, effectively eliminating harmful bacteria as well as combat other types of antibodies that attack healthy cells.

In most patients, hypergammaglobulinemia is marked by acute shortage of IgG antibodies, apart from high IgM levels. This form of treatment involves injecting IgG antibodies to improve immunity and combat infections.

In any case, the patient is advised to undergo a gamma globulin test, to check the range of different types of antibodies present in the blood. If the results show normal levels of IgG, then taking IgG replacement therapy will not be of any help.

So, according to the test result, a specific intravenous immunoglobulin infusion may be recommended to treat the condition. The doctor may also recommend antibiotics to enhance immunity.

Disclaimer: The information provided in this story is solely for educating the reader. It is not intended to be a substitute for the advice of a medical expert.